Abstract 5253: SOX2-mediated cell survival and chemoresistance in lung cancer.

Abstract

Abstract Tumor cells have long been observed to share several biological characteristics with normal stem/progenitor cells; however, the oncogenic mechanisms underlying the stemness features remain elusive. Here we report the involvement of BCL2L1 in SOX2-mediated cell survival and chemoresistance in lung cancer. SOX2 was associated with poor prognosis in lung cancer patients and was expressed in a subclass of lung cancer cells the survival and chemoresistance of which were dependent on SOX2 stem cell signaling. SOX2 promoted chemoresistance, and silencing of SOX2 perturbed mitochondrial function, causing marked apoptosis and autophagy. Moreover, SOX2 knockdown attenuated tumor growth in a xenograft mouse model. SOX2 induced BCL2L1 expression, the ectopic expression of which rescued the effects of SOX2 silencing on apoptosis, autophagy, and mitochondrial function. SOX2 and BCL2L1 expression levels were significantly correlated in human lung tumors, supporting the involvement of BCL2L1 in SOX2-mediated oncogenesis. Our findings reveal for the first time that SOX2-BCL2L1 signaling maintains mitochondrial integrity and enhances cell survival, leading to increased chemoresistance in lung cancer cells. Citation Format: Yu-Ting Chou, Chih-Chan Lee, Shih-Hsin Hsiao, Sey-En Lin, Sheng-Chieh Lin, Yuan-Hung Wang, Cheng-Wen Wu. SOX2-mediated cell survival and chemoresistance in lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5253. doi:10.1158/1538-7445.AM2013-5253